AMINOSYN®A Crystalline Amino Acid Solution

DESCRIPTION

Aminosyn® (a crystalline amino acid solution)
is a sterile, nonpyrogenic solution for intravenous infusion. Five different
formulations are available:

Aminosyn
Formulations

Essential
Amino Acids (mg/100 mL)

Aminosyn

3.5%

5%

7%

8.5%

10%

Isoleucine

252

360

510

620

720

Leucine

329

470

660

810

940

Lysine (acetate)*

252

360

510

624

720

Methionine

140

200

280

340

400

Phenylalanine

154

220

310

380

440

Threonine

182

260

370

460

520

Tryptophan

56

80

120

150

160

Valine

280

400

560

680

800

* Amount cited is for Lysine alone and does not include
the acetate salt.

Nonessential
Amino Acids (mg/100 mL)

Aminosyn

3.5%

5%

7%

8.5%

10%

Alanine

448

640

900

1100

1280

Arginine

343

490

690

850

980

Histidine

105

150

210

260

300

Proline

300

430

610

750

860

Serine

147

210

300

370

420

Tyrosine

31

44

44

44

44

Glycine

448

640

900

1100

1280

Aminosyn

3.5%

5%

7%

8.5%

10%

Electrolytes
(mEq/Liter)

Sodium (Na+)

7a

None

None

None

None

Potassium (K+)

None

5.4b

5.4b

5.4b

5.4b

Chloride (Cl−)

None

None

None

35c

None

Acetate (C2H3O2−)d

46

86

105

90

148

Protein Equivalent

(approx.
grams/liter)

35

50

70

85

100

Total Nitrogen

(grams/liter)

5.5

7.86

11.00

13.4

15.72

Osmolarity

(mOsmol/liter
calc.)

357

500

700

850

1000

pH and

range

5.4 (4.5 − 6.0e)

5.1 (4.5 − 6.0e)

5.3 (4.5 − 6.0e)

5.3 (4.5 − 6.0f)

5.4 (4.5 − 6.0e)

a Includes 7 mEq Na+/liter from the
antioxidant, sodium hydrosulfite.

b Includes
5.4 mEq K+/liter from the antioxidant, potassium metabisulfite.

c Includes
chloride from HCl added for processing and pH adjustment.

d Includes
acetate from acetic acid used in processing and from Lysine acetate.

e Adjusted
with acetic acid.

f Adjusted with acetic
acid and hydrochloric acid.

The formulations contain
the following added ingredients/100 mL:

Aminosyn 5%,
7%, 8.5% and 10%

Potassium metabisulfite added, 60 mg.

Aminosyn
3.5%

Sodium hydrosulfite added, 60 mg.

The
formulas for the individual amino acids present in Aminosyn (a crystalline
amino acid solution) are as follows:

Essential
Amino Acids

Isoleucine

(C6H13NO2)

Leucine

(C6H13NO2)

Lysine Acetate

(C6H14N2O2•
CH3COOH)

Methionine

(C5H11NO2S)

Phenylalanine

(C9H11NO2)

Threonine

(C4H9NO3)

Tryptophan

(C11H12N2O2)

Valine

(C5H11NO2)

Nonessential
Amino Acids

Alanine

(C3H7NO2)

Arginine

(C6H14N4O2)

Histidine

(C6H9N3O2)

Proline

(C5H9NO2)

Serine

(C3H7NO3)

Tyrosine

(C9H11NO3)

Glycine

(C2H5NO2)

CLINICAL PHARMACOLOGY

Aminosyn provides crystalline amino acids to promote protein
synthesis and wound healing, and to reduce the rate of endogenous protein
catabolism. Aminosyn, given by central venous infusion in combination with
concentrated dextrose, electrolytes, vitamins, trace metals, and ancillary
fat supplements, constitutes total parenteral nutrition (TPN). Aminosyn can
also be administered by peripheral vein with dextrose and maintenance electrolytes.
Intravenous fat emulsion may be substituted for part of the carbohydrate calories
during either TPN or peripheral vein administration of Aminosyn.

INDICATIONS AND USAGE

Aminosyn infused with dextrose by peripheral vein infusion
is indicated as a source of nitrogen in the nutritional support of patients
with adequate stores of body fat, in whom, for short periods of time, oral
nutrition cannot be tolerated, is undesirable, or inadequate.

SUPPLEMENTAL
ELECTROLYTES, IN ACCORDANCE WITH THE PRESCRIPTION OF THE ATTENDING PHYSICIAN,
MUST BE ADDED TO AMINOSYN SOLUTIONS WITHOUT ELECTROLYTES.

Aminosyn
can be administered peripherally with dilute (5 to 10%) dextrose solution
and I.V. fat emulsion as a source of nutritional support. This form of nutritional
support can help to preserve protein and reduce catabolism in stress conditions
where oral intake is inadequate.

When administered with
concentrated dextrose solutions with or without fat emulsions, Aminosyn is
also indicated for central vein infusion to prevent or reverse negative nitrogen
balance in patients where: (a) the alimentary tract, by the oral, gastrostomy
or jejunostomy route cannot or should not be used; (b) gastrointestinal absorption
of protein is impaired; (c) metabolic requirements for protein are substantially
increased as with extensive burns and (d) morbidity and mortality may be reduced
by replacing amino acids lost from tissue breakdown, thereby preserving tissue
reserves, as in acute renal failure.

CONTRAINDICATIONS

This preparation should not be used in patients with hepatic
coma or metabolic disorders involving impaired nitrogen utilization.

WARNINGS

Intravenous infusion of amino acids may induce a rise in
blood urea nitrogen (BUN), especially in patients with impaired hepatic or
renal function. Appropriate laboratory tests should be performed periodically
and infusion discontinued if BUN levels exceed normal postprandial limits
and continue to rise. It should be noted that a modest rise in BUN normally
occurs as a result of increased protein intake.

Administration
of amino acid solutions to a patient with hepatic insufficiency may result
in serum amino acid imbalances, metabolic alkalosis, prerenal azotemia, hyperammonemia,
stupor and coma.

Administration of amino acid solutions
in the presence of impaired renal function may augment an increasing BUN,
as does any protein dietary component.

Solutions containing
sodium ion should be used with great care, if at all, in patients with congestive
heart failure, severe renal insufficiency and in clinical states in which
there exists edema with sodium retention.

Solutions
which contain potassium ion should be used with great care, if at all, in
patients with hyperkalemia, severe renal failure and in conditions in which
potassium retention is present.

Solutions containing
acetate ion should be used with great care in patients with metabolic or respiratory
alkalosis. Acetate should be administered with great care in those conditions
in which there is an increased level or an impaired utilization of this ion,
such as severe hepatic insufficiency.

Hyperammonemia
is of special significance in infants, as it can result in mental retardation.
Therefore, it is essential that blood ammonia levels be measured frequently
in infants.

Instances of asymptomatic hyperammonemia
have been reported in patients without overt liver dysfunction. The mechanisms
of this reaction are not clearly defined, but may involve genetic defects
and immature or subclinically impaired liver function.

Aminosyn
can be infused simultaneously with fat emulsion by means of a Y-connector
located near the infusion site using separate flow rate controls for each
solution.

Aminosyn 5%, 7%, 8.5% and 10% contain potassium
metabisulfite; Aminosyn 3.5% contains sodium hydrosulfite, sulfites that may
cause allergic-type reactions including anaphylactic symptoms and life-threatening
or less severe asthmatic episodes in certain susceptible people. The overall
prevalence of sulfite sensitivity in the general population is unknown and
probably low. Sulfite sensitivity is seen more frequently in asthmatic than
in nonasthmatic people.

PRECAUTIONS

Special care must be taken when administering glucose to
provide calories in diabetic or prediabetic patients.

Because
of its antianabolic activity, concurrent administration of tetracycline may
reduce the potential anabolic effects of amino acids infused with dextrose
as part of a parenteral feeding regimen.

Feeding regimens
which include amino acids should be used with caution in patients with history
of renal disease, pulmonary disease, or with cardiac insufficiency so as to
avoid excessive fluid accumulation.

The effect of infusion
of amino acids, without dextrose, upon carbohydrate metabolism of children
is not known at this time.

Nitrogen intake should be
carefully monitored in patients with impaired renal function.

For
long-term total nutrition, or if a patient has inadequate fat stores, it is
essential to provide adequate exogenous calories concurrently with the amino
acids. Concentrated dextrose solutions are an effective source of such calories.
Such strongly hypertonic nutrient solutions should be administered through
an indwelling intravenous catheter with the tip located in the superior vena
cava.

SPECIAL PRECAUTIONS FOR CENTRAL
INFUSIONS

ADMINISTRATION BY CENTRAL VENOUS
CATHETER SHOULD

BE USED ONLY BY THOSE FAMILIAR WITH
THIS TECHNIQUE

AND ITS COMPLICATIONS.

Central vein infusion (with added concentrated carbohydrate
solutions) of amino acid solutions requires a knowledge of nutrition as well
as clinical expertise in recognition and treatment of complications. Attention
must be given to solution preparation, administration and patient monitoring.
IT IS ESSENTIAL THAT A CAREFULLY PREPARED PROTOCOL BASED ON CURRENT MEDICAL
PRACTICES BE FOLLOWED, PREFERABLY BY AN EXPERIENCED TEAM.

The placement of a central venous catheter should be regarded as a surgical
procedure. One should be fully acquainted with various techniques of catheter
insertion. For details of technique and placement sites, consult the medical
literature. X-ray is the best means of verifying catheter placement. Complications
known to occur from the placement of central venous catheters are pneumothorax,
hemothorax, hydrothorax, artery puncture and transection, injury to the brachial
plexus, malposition of the catheter, formation of arteriovenous fistula, phlebitis,
thrombosis and air and catheter emboli.

Septic:

The
constant risk of sepsis is present during administration of total parenteral
nutrition. It is imperative that the preparation of the solution and the placement
and care of catheters be accomplished under strict aseptic conditions.

Solutions should ideally be prepared in the hospital pharmacy in a laminar
flow hood using careful aseptic technique to avoid inadvertent touch contamination.
Solutions should be used promptly after mixing. Storage should be under refrigeration
and limited to a brief period of time, preferably less than 24 hours.

Administration
time for a single bottle and set should never exceed 24 hours.

Metabolic:

The
following metabolic complications have been reported: Metabolic acidosis and
alkalosis, hypophosphatemia, hypocalcemia, osteoporosis, glycosuria, hyperglycemia,
hyperosmolar nonketotic states and dehydration, rebound hypoglycemia, osmotic
diuresis and dehydration, elevated liver enzymes, hypo- and hypervitaminosis,
electrolyte imbalances and hyperammonemia in children. Frequent evaluations
are necessary especially during the first few days of therapy to prevent or
minimize these complications.

Administration of glucose
at a rate exceeding the patient’s utilization rate may lead to hyperglycemia,
coma and death.

Pregnancy Category C.

Animal reproduction studies have not been conducted with
Aminosyn. It is not known whether Aminosyn can cause fetal harm when administered
to a pregnant woman or can affect reproduction capacity. Aminosyn should be
given to a pregnant woman only if clearly needed.

Geriatric Use

Clinical studies of Aminosyn have not been performed to determine
whether patients over 65 years respond differently from younger subjects.
Other reported clinical experience has not identified differences in responses
between elderly and younger patients. In general, dose selection for elderly
patients should be cautious, reflecting the greater frequency of decreased
hepatic, renal, or cardiac function, and of concomitant disease or other drug
therapy. This drug is known to be substantially excreted by the kidney, and
the risk of toxic reactions to this drug may be greater in patients with impaired
renal function. Because elderly patients are more likely to have decreased
renal function, care should be taken in dose selection, and it may be usefulto monitor renal functions.

CLINICAL EVALUATION AND
LABORATORY DETERMINATIONS, AT THE DISCRETION OF THE ATTENDING PHYSICIAN, ARE
NECESSARY FOR PROPER MONITORING DURING ADMINISTRATION. Do not withdraw venous
blood for blood chemistries through the peripheral infusion site, as interference
with estimations of nitrogen containing substances may occur. Blood studies
should include glucose, urea nitrogen, serum electrolytes, ammonia, cholesterol,
acid-base balance, serum proteins, kidney and liver function tests, osmolarity
and hemogram. White blood count and blood cultures are to be determined if
indicated. Urinary osmolality and glucose should be determined as necessary.

ADVERSE REACTIONS

Peripheral Infusions

A
4.25 or 5% solution of amino acids (without additives) is slightly hypertonic.
A 3.5% concentration of amino acids (without additives) is slightly hypertonic.
Local reactions consisting of a warm sensation, erythema, phlebitis and thrombosis
at the infusion site have occurred with peripheral intravenous infusion of
amino acids particularly if other substances, such as antibiotics, are also
administered through the same site. In such cases the infusion site should
be changed promptly to another vein. Use of large peripheral veins, inline
filters, and slowing the rate of infusion may reduce the incidence of local
venous irritation. Electrolyte additives should be spread throughout the day.
Irritating additive medications may need to be injected at another venous
site.

Generalized flushing, fever and nausea also have
been reported during peripheral infusions of amino acid solutions.

OVERDOSAGE

In the event of overhydration or solute overload, re-evaluate
the patient and institute appropriate corrective measures. See WARNINGS and
PRECAUTIONS.

DOSAGE AND ADMINISTRATION

The total daily dose of the solution depends on the daily
protein requirements and on the patient’s metabolic and clinical response.
In many patients, provision of adequate calories in the form of hypertonic
dextrose may require the administration of exogenous insulin to prevent hyperglycemia
and glycosuria. To prevent rebound hypoglycemia, a solution containing 5%
dextrose should be administered when hypertonic dextrose infusions are abruptly
discontinued.

Parenteral drug products should be inspected
visually for particulate matter and discoloration prior to administration,
whenever solution and container permit.

Peripheral Vein Nutritional
Maintenance

Aminosyn® 3.5%
(a crystalline amino acid solution) together with dextrose in concentrations
of 5% to 10% is suitable for administration by peripheral vein. This solution
is not intended for central vein infusion since it does not contain adequate
amounts of amino acids or electrolytes for administration with high concentrations
of dextrose. Aminosyn 7%, 8.5% or 10% may be diluted with sterile water for
injection or 5 to 10% Dextrose Injection to achieve a final amino acid concentration
of 3.5, 4.25 or 5% for peripheral administration.

For
peripheral intravenous infusion, 1.0 to 1.5 g/kg/day of total amino acids
will reduce protein catabolism. Infusion or ingestion of carbohydrate or lipid
will not reduce the nitrogen sparing effect of intravenous amino acid infusions
at this dose.

As with all intravenous fluid therapy,
the primary aim is to provide sufficient water to compensate for insensible,
urinary and other (nasogastric suction, fistula drainage, diarrhea) fluid
losses. Total fluid requirements, as well as electrolyte and acid-base needs,
should be estimated and appropriately administered.

For
an amino acid solution of specified total concentration, the volume required
to meet amino acid requirements per 24 hours can be calculated. After making
an estimate of the total daily fluid (water) requirement, the balance of fluid
needed beyond the volume of amino acid solution required can be provided either
as a noncarbohydrate or a carbohydrate-containing electrolyte solution. I.V.
lipid emulsion may be substituted for part of the carbohydrate containing
solution. Vitamins and additional electrolytes as needed for maintenance or
to correct imbalances may be added to the amino acid solution.

If
desired, only one-half of an estimated daily amino acid requirement of 1.5
g/kg can be given on the first day. Amino acids together with dextrose in
concentrations of 5% to 10% infused into a peripheral vein can be continued
while oral nutrition is impaired. However, if a patient is unable to take
oral nourishment for a prolonged period of time, institution of total parenteral
nutrition with exogenous calories should be considered.

Central Vein Total Parenteral
Nutrition

For central vein infusion with concentrated
dextrose solution, alone or with I.V. lipid, the total daily dose of the amino
acid solution depends upon daily protein requirements and the patient’s
metabolic and clinical response. The determination of nitrogen balance and
accurate daily body weights, corrected for fluid balance, are probably the
best means of assessing individual protein requirements.

ADULTS

Solutions
containing 3.5 to 5% amino acids with 5 to 10% glucose may be coinfused with
a fat emulsion by peripheral vein to provide approximately 1400 to 2000 kcal/day.
Fat emulsion coadministration should be considered when prolonged parenteral
nutrition is required in order to prevent essential fatty acid deficiency
(E.F.A.D.). Serum lipids should be monitored for evidence of EFAD in patients
maintained on fat-free total parenteral nutrition.

Aminosyn
5%, 7% (with or without electrolytes), 8.5% and 10% solutions should only
be infused via a central vein when admixed with sufficient dextrose to provide
full caloric requirements in patients who require prolonged total parenteral
nutrition. I.V. lipid may be administered separately to provide part of the
calories, if desired.

Total parenteral nutrition (TPN)
may be started with 10% dextrose added to the calculated daily requirement
of amino acids (1.5 g/kg for a metabolically stable patient). Dextrose content
is gradually increased over the next few days to the estimated daily caloric
need as the patient adapts to the increasing amounts of dextrose. Each gram
of dextrose provides approximately 3.4 kcal. Each gram of fat provides 9 kcal.

The
average depleted major surgical patient with complications requires between
2500 and 4000 kcal and between 12 and 24 grams of nitrogen per day. An adult
patient in an acceptable weight range with restricted activity who is not
hypermetabolic, requires about 30 kcal/kg of body weight/day. Average daily
adult fluid requirements are between 2500 and 3000 mL and may be much higher
with losses from fistula drainage or severe burns. Typically, a hospitalized
patient may lose 12 to 18 grams of nitrogen a day, and in severe trauma the
daily loss may be 20 to 25 grams or more.

Aminosyn
solutions without electrolytes are intended for patients requiring individualized
electrolyte therapy. Sodium, chloride, potassium, phosphate, calcium and magnesium
are major electrolytes which should be added to Aminosyn as required.

SERUM
ELECTROLYTES SHOULD BE MONITORED AS INDICATED. Electrolytes may be added to
the nutrient solution as indicated by the patient’s clinical condition
and laboratory determinations of plasma values. Major electrolytes are sodium,
chloride, potassium, phosphate, magnesium and calcium. Vitamins, including
folic acid and vitamin K are required additives. The trace element supplements
should be given when long-term parenteral nutrition is undertaken.

Calcium
and phosphorus are added to the solution as indicated. The usual dose of phosphate
added to a liter of TPN solution (containing 25% dextrose) is 12 mM. This
requirement is related to the carbohydrate calories delivered. Iron is added
to the solution or given intramuscularly in depot form as indicated. Vitamin
B12, vitamin K and folic acid are given intramuscularly or added
to the solution as desired.

Calcium and phosphate additives
are potentially incompatible when added to the TPN admixture. However, if
one additive is added to the amino acid bottle, and the other to the bottle
of concentrated dextrose, and if the contents of both bottles are swirled
before they are combined, then the likelihood of physical incompatibility
is reduced.

In patients with hyperchloremic or other
metabolic acidosis, sodium and potassium may be added as the acetate or lactate
salts to provide bicarbonate alternates.

In adults,
hypertonic mixtures of amino acids and dextrose may be safely administered
by continuous infusion through a central venous catheter with the tip located
in the vena cava. Typically, the 7%, 8.5% or 10% solution is used in equal
volume with 50% dextrose to provide an admixture containing 3.5%, 4.25% or
5% amino acids and 25% dextrose.

The rate of intravenous
infusion initially should be 2 mL/min and may be increased gradually. If administration
should fall behind schedule, no attempt to “catch up” to planned
intake should be made. In addition to meeting protein needs, the rate of administration
is governed by the patient’s glucose tolerance estimated by glucose
levels in blood and urine.

Aminosyn 10% solution, when
mixed with an appropriate volume of concentrated dextrose, offers a higher
concentration of calories and nitrogen per unit volume. This solution is indicated
for patients requiring larger amounts of nitrogen than could otherwise be
provided or where total fluid load must be kept to a minimum, for example,
patients with renal failure.

Provision of adequate calories
in the form of hypertonic dextrose may require exogenous insulin to prevent
hyperglycemia and glycosuria. To prevent rebound hypoglycemia, do not abruptly
discontinue administration of nutritional solutions.

PEDIATRIC

Pediatric
requirements for parenteral nutrition are constrained by the greater relative
fluid requirements of the infant and greater caloric requirements per kilogram.
Amino acids are probably best administered in a 2.5% concentration. For most
pediatric patients on intravenous nutrition, 2.5 grams amino acids/kg/day
with dextrose alone or with I.V. lipid calories of 100 to 130 kcal/kg/day
is recommended. In cases of malnutrition or stress, these requirements may
be increased. It is acceptable in pediatrics to start with a nutritional solution
of half strength at a rate of about 60 to 70 mL/kg/day. Within 24 to 48 hours
the volume and concentration of the solution can be increased until the full
strength pediatric solution (amino acids and dextrose) is given at a rate
of 125 to 150 mL/kg/day.

Supplemental electrolytes and
vitamin additives should be administered as deemed necessary by careful monitoring
of blood chemistries and nutritional status. Addition of iron is more critical
in the infant than the adult because of the increasing red cell mass required
for the growing infant. Serum lipids should be monitored for evidence of essential
fatty acid deficiency in patients maintained on fat-free TPN. Bicarbonate
should not be administered during infusion of the nutritional solution unless
deemed absolutely necessary.

To insure the precise delivery
of the small volumes of fluid necessary for total parenteral nutrition in
infants, accurately calibrated and reliable infusion systems should be used.

A
basic solution for pediatric use should contain 25 grams of amino acids and
200 to 250 grams of glucose per 1000 mL, administered from bottles containing
250 or 500 mL. Such a solution given at the rate of 145 mL/kg/day provides
130 kcal/kg/day.

HOW SUPPLIED

List No.

Concentration

Container
(mL)

2989

Aminosyn® 3.5%

1000

2990

Aminosyn® 5%

1000

500

250

2992

Aminosyn® 7%

1000

500

5855

Aminosyn® 8.5%

1000

500

2991

Aminosyn® 10%

1000*

500

*Provides sufficient volume to withdraw 1050 mL.

Exposure
of pharmaceutical products to heat should be minimized. Avoid excessive heat.
Protect from freezing. It is recommended that the product be stored at room
temperature (25°C); however, brief exposure up to 40°C does not
adversely affect the product. Avoid exposure to
light.